Serum Albumin Stimulates Protein Kinase G-dependent Microneme Secretion in Toxoplasma gondii

J Biol Chem. 2016 Mar 1. pii: jbc.M115.700518. [Epub ahead of print]

Brown KM¹, Lourido S², Sibley LD³.

Microneme secretion is essential for motility, invasion, and egress in apicomplexan parasites. Although previous studies indicate that Ca2+ and cGMP control microneme secretion, little is known about how these pathways are naturally activated. Here we have developed genetically-encoded indicators for Ca2+ and microneme secretion to better define the signaling pathways that regulate these processes in Toxoplasma gondii. We found that microneme secretion was triggered in vitro by exposure to a single host protein, serum albumin. The natural agonist serum albumin induced microneme secretion in a protein kinase G-dependent manner that correlated with increased cGMP levels. Surprisingly, serum albumin acted independently of elevated Ca2+ and yet it was augmented by artificial agonists that raise Ca2+, such as ethanol. Furthermore, although ethanol elevated intracellular Ca2+, it alone was unable to trigger secretion without the presence of serum or serum albumin. This dichotomy was recapitulated by zaprinast, a phosphodiesterase inhibitor that elevated cGMP and separately increased Ca2+ in a protein kinase G-independent manner leading to microneme secretion. Taken together, these findings reveal that microneme secretion is centrally controlled by protein kinase G and that this pathway is further augmented by elevation of intracellular Ca2+.
Copyright © 2016, The American Society for Biochemistry and Molecular Biology.

KEYWORDS:

calcium; calcium imaging; calcium intracellular release; cyclic GMP (cGMP); protein kinase G (PKG); protein secretion; second messenger

PMID:

26933037

[PubMed - as supplied by publisher]